Abstract
This article discusses the advantages and disadvantages of tricyclic antide-pressants (TCAs), tetracyclic antidepressants (i.e. mianserin), selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), triazolopyridines (i.e. trazodone), phenylpiperazines (i.e. nefazodone), serotonin and noradrenaline (norepinephrine) reuptake inhibitors (i.e. venlafaxine), and aminoketones [i.e. amfebutamone (bupropion)] in the treatment of late-life depression. A limitation of the existing literature is that most data regarding drugs are derived from studies that have involved medically stable outpatients who do not have dementia and who are less than 80 years of age. There is a paucity of data on the use of antidepressants in very elderly individuals, patients who have significant medical comorbity and patients with dementia or other neurological problems.
No one class of antidepressant has been found to be more effective than another in the acute treatment of geriatric major depression. However, given design shortcomings in many of these studies, the possibility of a real difference in efficacy between drugs (especially in the treatment of severe or melancholic depression) cannot be excluded. With respect to adverse effects, drug interactions, and dosage and administration, each class of antidepressant has its benefits and limitations. There is no one ‘first-line’ antidepressant for elderly patients with depression. Selection of an antidepressant should be made on a case by case basis, taking into account each patient’s characteristics.
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References
Blazer DG. Epidemiology of late-life depression. In: Schneider LS, Reynolds CF, Lebowitz BD, et al., editors. Diagnosis and treatment of depression in late life. Washington, DC: American Psychiatric Press; 1994: 9–19
NTH Consensus Development Panel. Diagnosis and treatment of depression in late life. JAMA 1992; 268: 1018–24
Crome P. Drug compliance in the elderly. In: Wheatley D, editor. Psychopharmacology of old age. Oxford: Oxford University Press; 1982: 55–64
Reynolds CF, Frank E, Kupfer DJ, et al. Treatment outcome in recurrent major depression: a post hoc comparison of elderly (‘young old’) and midlife patients. Am J Psychiatry 1996; 153: 1288–92
Gerson SC, Plotkin DA, Jarvik LF. Antidepressant drug studies, 1964–1986: empirical evidence for aging patients. J Clin Psychopharmacol 1988; 8: 311–22
Volz HP, Möller HJ. Antidepressant drug therapy in the elderly: a critical review of the controlled clinical trials conducted since 1980. Pharmacopsychiatry 1994; 27: 93–100
Anstey K, Brodaty H. Antidepressants and the elderly: double-blind trials 1987–1992. Int J Geriatr Psychiatry 1995; 10: 265–79
Menting JEA, Honig A, Verhey FRJ, et al. Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects. Int Clin Psychopharmacol 1996; 11: 165–75
Schneider LS. Pharmacologic considerations in the treatment of late-life depression. Am J Geriatr Psychiatry 1996; 4Suppl. 1: S51–S65
Mittmann N, Herrmann N, Einarson TR, et al. The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis. J Affect Disord 1997; 46: 191–217
Mahapatra SN, Hackett D. A randomized, double-blind, parallel-group comparison of venlafaxine and dothiepin in geriatric patien’ts with major depression. Int J Clin Pract 1997; 51: 209–13
Preskorn S, Burke M. Somatic therapy for major depressive disorder: selection of an antidepressant. J Clin Psychiatry 1992; 53Suppl. 9: 1–14
Danish University Antidepressant Group (DUAG). Citalopram: clinical effect profile in comparison with clomipramine: a controlled multicenter study. Psychopharmacology 1986; 90: 131–8
Danish University Antidepressant Group (DUAG). Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect, than clomipramine in a controlled multicenter study. J Affect Disord 1990; 18: 289–99
Danish University Antidepressant Group (DUAG). Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disord 1993; 28: 105–16
Perry PJ. Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord 1996; 39: 1–6
Roose SP, Glassman AH, Attia E, et al. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry 1994; 151: 1735–9
Georgotas A, McCue RE, Cooper TB, et al. How effective and safe is continuation therapy in elderly depressed patients? Arch Gen Psychiatry 1988; 45: 929–32
Georgotas A, McCue RE, Cooper TB. A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients. Arch Gen Psychiatry 1989; 46: 783–6
Reynolds CF, Frank E, Perel JM, et al. Maintenance therapies for late-life recurrent major depression: research and review circa 1995. Int Psychogeriatr 1995; 7 Suppl.: 27–39
Old Age Depression Interest Group. How long should the elderly take antidepressants? A double-blind placebo-controlled study of continuation/prophylaxis therapy with dothiepin. Br J Psychiatry 1993; 162: 175–82
Georgotas A, McCue RE, Hapworth W, et al. Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly. Biol Psychiatry 1986; 21: 1155–66
Miller MD, Pollock BG, Rifai AH, et al. Longitudinal analysis of nortriptyline side effects in elderly depressed patients. J Geriatr Psychiatry Neurol 1991; 4: 226–30
Reynolds CF, Frank E, Perel JM, et al. Nortriptyline side effects during double-blind, randomised, placebo-controlled maintenance therapy in older depressed patients. Am J Geriatr Psychiatry 1995; 3: 170–5
Rosen J, Sweet R, Pollock BG, et al. Nortriptyline in the hospitalized elderly: tolerance and side effect reduction. Psychopharmacol Bull 1993; 29(2): 327–31
Katz IR, Simpson GM, Curlick SM, et al. Pharmacologic treatment of major depression for elderly patients in residential care settings. J Clin Psychiatry 1990; 51Suppl. 7: 41–7
Lipsey JR, Robinson RG, Pearlson GD, et al. Nortriptyline treatment of post-stroke depression: a double-blind study. Lancet 1984; I: 297–300
Koenig HG, Breitner JCS. Use of antidepressants in medically ill older patients. Psychosomatics 1990; 31: 22–32
Young RC, Mattis S, Alexopoulos GS, et al. Verbal memory and plasma drug concentrations in elderly depressives treated with nortriptyline. Psychopharmacol Bull 1991; 27(3): 291–4
Meyers BS, Mattis S, Gabriele M, et al. Effects of nortriptyline on memory self-assessment and performance in recovered elderly depressives. Psychopharmacol Bull 1991; 27(3): 295–9
Hoff AL, Shukla S, Helms P, et al. The effects of nortriptyline on cognition in elderly depressed patients. J Clin Psychopharmacol 1990; 10(3): 231–2
Halper JP, Mann JJ. Cardiovascular effects of antidepressant medications. Br J Psychiatry 1988; 153Suppl. 3: 87–98
Roose SP, Glassman AH, Giardina EGV, et al. Nortriptyline in depressed patients with left ventricular impairment. JAMA 1986; 256: 3253–7
Roose SP, Dalack GW. Treating the depressed patient with cardiovascular problems. J Clin Psychiatry 1992; 53Suppl 9.: 25–31
Roose SP, Glassman AH. Antidepressant choice in the patient with cardiac disease: lessons from the cardiac arrhythmia suppression trial (CAST) studies. J Clin Psychiatry 1994; 55 (9 Suppl. A): 83–7
Preskorn SH. Recent pharmacologic advances in antidepressant therapy for the elderly. Am J Med 1993; 94(Suppl. 5A): 2–12S
Rockwell E, Lam RW, Zisook S. Antidepressant drug studies in the elderly. Psychiatr Clin North Am 1988; 11: 215–33
Sallee FR, Pollock BG. Clinical pharmacokinetics of imipramine and desipramine. Clin Pharmacokinet 1990; 18: 346–64
von Moltke LL, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of antidepressants in the elderly. Clin Pharmacokinet 1993; 24: 141–60
Rolan PE. Plasma protein binding displacement interactions: why are they still regarded as clinically important? Br J Clin Pharmacol 1994; 37: 125–8
Pollock BG, Perel JM, Paradis CF, et al. Metabolic and physiologic consequences of nortriptyline treatment in the elderly. Psychopharmacol Bull 1994; 30(2): 145–50
Crewe HK, Lennard MS, Tucker GT, et al. The effect of selective serotonin re-uptake inhibitors on cytochrome P450 2D6 (CYP 2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992: 34: 262–5
Wakeling A. Efficacy and side effects of mianserin, atetracyclic antidepressant. Postgrad Med J 1983; 59: 229–31
Kerr JS, Sherwood N, Hindmarch I. The comparative psychopharmacology of 5HT reuptake inhibitors. Hum Psychopharmacol 1991; 6: 313–7
Macquire KP, Norman TR, Burrows GD, et al. A pharmacokinetic study of mianserin. Eur J Clin Pharmacol 1982; 21: 517–22
Leinonen E, Koponen H, Lepola U. Serum mianserin and ageing. Prog Neuropsychopharmacol, Biol Psychiatry 1994; 18: 833–45
Shami M, Elliot HL, Kelman AT, et al. The pharmacokinetics of mianserin. Br J Clin Pharmacol 1983; 15: 313S–22S
Begg EG, Sharman JR, Kidd JE, et al. Variability in the elimination of mianserin in elderly patients. Br J Clin Pharmacol 1989; 27: 445–51
Sasa H. Steady state plasma kinetics of mianserin and its major metabolite desmethylmianserin. Jpn J Neuropsychopharmacology 1992; 14: 441–8
Goodnick PJ. Pharmacokinetic optimisation of therapy with newer antidepressants. Clin Pharmacokinet 1994; 27: 307–30
Thomas DR, Nelson DR, Johnson AM. Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology 1987; 93: 193–200
Geretsegger C, Bohmer F, Ludwig M. Paroxetine in the elderly depressed patient: randomised comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol 1994; 9: 25–9
Grimsley SR, Jann MW. Paroxetine, sertraline and fluvoxamine: new selective serotonin reuptake inhibitors. Clin Pharm 1992; 11: 930–57
Sheehan D, Dunbar GC, Fuell DL. The effect of paroxetine on anxiety and agitation associated with depression. Psychopharmacol Bull 1992; 28: 139–43
Tollefson GD, Greist JH, Jefferson JW, et al. Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. J Clin Psychopharmacol 1994; 14: 385–91
Rickeis K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. J Clin Psychiatry 1990; 51 (12 Suppl. B): 9–12
Brown WA, Harrison W. Are patients who are intolerant to one serotonin selective reuptake inhibitor intolerant to another? J Clin Psychiatry 1995; 56: 30–4
Laghrissi-Thode F, Pollock BG, Miller M, et al. Comparative effects of sertraline and nortriptyline on body sway in older depressed patients. Am J Geriatr Psychiatry 1995; 3: 217–28
Liu BA, Mittmann N, Knowles SR, et al. Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports. Can Med Assoc J 1996; 155: 519–27
Flint AJ, Crosby J, Genik JL. Recurrent hyponatremia associated with fluoxetine and paroxetine [letter]. Am J Psychiatry 1996; 153: 134
Mattila MJ, Saarialho-Kere U, Mattila M. Acute effects of sertraline, amitriptyline, and placebo on the psychomotor performance of healthy subjects over 50 years of age. J Clin Psychiatry 1988; 49(8 Suppl.): 52–8
Hindmarch I, Shillingford J, Shillingford C. The effects of sertraline on psychomotor performance in elderly volunteers. J Clin Psychiatry 1990; 51 (12 Suppl. B): 34–6
Hindmarsh I, Kerr JS. Effects of paroxetine on cognitive function in depressed patients, volunteers and elderly volunteers. Med Sci Res 1994; 22: 669–70
McEntee W, Oxman T, Ko G, et al. The effects of sertraline on cognition in depressed geriatric patients [abstract]. Psychopharmacol Bull 1996; 32(3): 486
Sheline YI, Freedland KE, Carney RM. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease? Am J Med 1997; 102: 54–9
Roose SP, Laghrissi-Thode F, Kennedy JS, et al. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA 1998; 279: 287–91
Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996; 153: 311–20
Shader RI, von Moltke LL, Schmider J, et al. The clinician and drug interactions: an update. J Clin Psychopharmacol 1996; 16: 197–201
Harvey AT, Preskorn SH. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors: part II. J Clin Psychopharmacol 1996; 16: 345–55
Newhouse PA. Use of serotonin selective reuptake inhibitors in geriatric depression. J Clin Psychiatry 1996; 57Suppl. 5: 12–22
Rifkin A. SSRI optimal dose remains at issue. J Clin Psychiatry 1997; 58: 87–8
De Vane CL. Pharmacokinetics of the selective serotonin reuptake inhibitors. J Clin Psychiatry 1992; 53Suppl. 2: 13–20
Thase ME, Trivedi MH, Rush AJ. MAOIs in the contemporary treatment of depression. Neuropsychopharmacology 1995; 12: 185–219
Mallinger AG, Smith F. Pharmacokinetics of monoamine oxidase inhibitors. Psychopharmacol Bull 1991; 27: 493–502
Gardner DM, Shulman KI, Walker SE, et al. The making of a user friendly MAOI diet. J Clin Psychiatry 1996; 57(3): 99–104
Flint AJ, Rifat SL. The effect of sequential antidepressant treatment on geriatric depression. J Affect Disord 1996; 36: 95–105
Georgotas A, Friedman E, McCarthy M, et al. Resistant geriatric depressions and therapeutic response to monoamine oxidase inhibitors. Biol Psychiatry 1983; 18(2): 195–205
Sunderland T, Cohen RM, Molchan S, et al. High-dose selegiline in treatment-resistant older depressive patients. Arch Gen Psychiatry 1994; 51: 607–15
Nair NPV, Ahmed SK, Ng Ying Kin NMK, et al. Reversible and selective inhibitors of monoamine oxidase A in the treatment of depressed elderly patients. Acta Psychiatr Scand 1995; 91Suppl. 386: 28–35
Moll E, Hetzel W. Moclobemide safety in depressed patients. Acta Psychiatr Scand 1990; 82Suppl. 360: 69–70
Wesnes KA, Simpson PM, Christmas L, et al. The effects of moclobemide on cognition. J Neural Transm 1989; 28 Suppl.: 91–102
Anand R, Wesnes KA. Cognition-enhancing effects of moclobemide, a reversible MAO-inhibitor, in humans. Adv Neurol 1990; 51: 261–8
Gram LF, Guentert TW, Grange S, et al. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: a panel study. Clin Pharmacol Ther 1995; 57: 670–7
Stoeckel K, Pfefen JP, Mayersohn M, et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. Acta Psychiatr Scand 1990; 82Suppl. 360: 94–7
Nair NPV, Amin M, Holm P, et al. Moclobemide and nortriptyline in elderly depressed patients: a randomized, multicenter trial against placebo. J Affect Disord 1995; 33: 1–9
Georgotas A, Thomas L, Forsell TL, et al. Trazodone hydrochloride: a wide spectrum antidepressant with a unique pharmacological profile: a review of its neurochemical effects, pharmacology, clinical efficacy, and toxicology. Pharmacotherapy 1982; 2: 255–64
Murphy DL, Mueller EA, Hill JL, et al. Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology 1989; 98: 275–82
Barbhaiya RH, Buch AB, Greene DS. Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan. Br J Pharmacol 1996; 42: 573–81
Nutt D. Early action of nefazodone in anxiety associated with depression. J Psychopharmacol 1996; 10Suppl. 1: 18–21
Baldwin DS, Hawley CJ, Abed RT, et al. A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate-to-severe depression. J Clin Psychiatry 1996; 57Suppl. 2: 46–52
Robinson DS, Roberts DL, Smith JM, et al. The safety profile of nefazodone. J Clin Psychiatry 1996; 57Suppl. 2: 31–8
van Laar MW, van Willigenburg APP, Volkerts ER. Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adults and elderly subjects. J Clin Psychopharmacol 1995; 15: 30–40
Barbhaiya RH, Buch AB, Greene DS. A study of the effect of age and gender on the pharmacokinetics of nefazodone after single and multiple doses. J Clin Psychopharmacol 1996; 16: 19–25
Feighner JP. The role of venlafaxine in rational antidepressant therapy. J Clin Psychiatry 1994; 55 (9 Suppl. A): 62–8
Rudorfer MV, Potter WZ. Antidepressants: a comparative review of the clinical pharmacology and therapeutic use of the ‘newer’ versus the ‘older’ drugs. Drugs 1989; 37: 713–38
Rudorfer MV, Potter WZ. The role of metabolites of antidepressants in the treatment of depression. CNS Drugs 1997; 7(4): 273–312
Sweet RA, Pollock BG, Kirshner M, et al. Pharmacokinetics of single- and multiple- dose bupropion in elderly patients with depression. J Clin Pharmacol 1995; 35: 876–84
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Flint, A.J. Choosing Appropriate Antidepressant Therapy in the Elderly. Drugs & Aging 13, 269–280 (1998). https://doi.org/10.2165/00002512-199813040-00003
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DOI: https://doi.org/10.2165/00002512-199813040-00003